Due to their essential role in the regulation of all physiological metabolic pathways, proteins can be useful drugs (as both agonists and/or antagonists) for the treatment of a variety of physiological disorders or diseases. The biological activity of proteins is often mediated by the distinct conformations that they exist in or are able to access. Thus, for example, proteins exhibit structural motifs, known as secondary structure, which include various turn (e.g. gamma- and beta-turns), sheet (beta sheet) and helical (alpha helix and pi helix) conformations. However, limitations in the size of molecules allowed into cells through naturally occurring non-invasive transduction pathways (e.g. endocytosis) generally limits or precludes the use of whole proteins as drugs. Consequently, short peptide sequences containing the functional domain(s) of the whole protein are preferred drug candidates.
Proteins can also be the targets of small molecule drugs. Designing small molecule drugs often involves assaying the activity of the drug candidates against shorter peptide sequences containing the functional domain(s) of the whole protein target. In both cases, because short peptide sequences often lack sufficient binding interactions (e.g., hydrogen bonding interactions, solvophobic interactions, electrostatic interactions, disulphide bonds, etc.), they are unable to access the same native, folded conformations when removed from the whole protein, thereby limiting their usefulness as drugs or drug targets.